The present invention relates generally to the area of delivery of materials, for intracellular therapeutics or diagnosis. More particularly, the present invention provides magnetic nanoparticles, a method for making the particles, and a method for using the particles in the treatment of cancer using a DC magnetic field.
In the past 30 years, major advances have been made in the diagnosis and treatment of human malignancies. In parallel, biotechnologies and nanotechnologies have provided avenues for the development of novel approaches to treatment of human diseases. Currently, chemotherapy is a widely used method of treatment for many cancers, but it has some distinct limitations and disadvantages. The main disadvantage of chemotherapy is related to drug toxicity, which severely restricts the drug dosages that can be used to effect eradication of the cancerous cells. To provide a more effective chemotherapeutic approach, one area of research has focused on specific targeting of chemotherapeutic objects to the cancer cells (Schally et al., 1999, J. Endocrinol., 141:1; Nagy et al., 1996, Proc. Natl. Acad. Sci., USA, 93:7269; Emons et al., 1993, J. Clin. Endocrinol. Metab., 77:1458). Thus, cancerous cells may be targeted based on district molecules on the cells surface.
Since 1950, magnetic probes and particles have been investigated as a potential treatment for cancer. Studies demonstrate that the hyperthermia (Grittner et al., 1997, Hybridoma, 16:109; Higler et al., 1997, Invest. Radiol., 32:705) generated by magnetic particles coupled to a high frequency AC magnetic field (requiring a tremendous power) could be used as an alternate or an adjuvant to therapy for cancer treatment. The hyperthermic activity (heat produced by the relaxation magnetic energy of the magnetic material) was shown to effectively destroy tumor tissue surrounding the probes or particles. The development of ultra-small magnetic particles (ferrofluids) with high crystallinity provided the next step in magnetically induced hyperthermic therapy. This treatment resulted in reduction of tumor size when the particles are directly injected into the tissue. However, no specificity was shown using such therapy. Thus, there is an ongoing need to develop specific targeting of magnetic nanoproducts.
The present invention provides novel nanosized (less than 100 nm) particles termed as xe2x80x9cnanoclinicsxe2x80x9d or xe2x80x9cnanoparticlesxe2x80x9d or xe2x80x9cnanobubblesxe2x80x9d for therapeutic or diagnostic use. The particles have a core of a therapeutic or diagnostic material surrounded by a shell composed of a bio-compatible material. Further, the nanoparticles contain a targeting agent on the surface of the shell for specific recognition of targeted cells. The nanoparticles optionally contain a tracking agent.
The present invention also provides a method for the selective destruction of targeted cells, such as cancerous cells. Upon exposure of the cells to nanoclinics having a magnetic core, cells containing molecules having specific affinity for the targeting agent will attach and/or internalize the nanoclinics. Subsequent application of a DC magnetic field can specifically destroy the targeted cells.
The present invention also provides a method for the preparation of the nanoparticles. The method comprises the steps of forming iron oxide core, forming a silica shell around the iron oxide core and attaching one or more targeting agents to the shell via carbon spacers. A tracking dye may be attached to the iron oxide core so as to be able to track the nanoparticles.